Over the last several decades, testicular cancer rates have been rapidly increasing in the United States, as well as in other countries. Testicular cancer has now become the most common malignancy in young men. Little is known about the etiology of the observed increases in testicular cancer incidence. Several recent studies suggest that environmental exposure to organochlorines, such as polychlorinated biphenyls (PCBs) and chlorinated pesticides, may increase testicular cancer risk. This relationship is biologically plausible since many organochlorines possess hormonal activities and are suspected or probable human carcinogens. The proposed case-control study of testicular cancer in Connecticut and Massachusetts will investigate the hypotheses that: 1) exposure to organochlorine compounds increases testicular cancer risk; and 2) risk of testicular cancer associated with organochlorine exposure is modified by major genes which have been associated with either the regulation, metabolism, or functional activities of endogenous and exogenous hormones. Cases will consist of 800 (300 from Connecticut and 500 from Massachusetts) histologically confirmed incident testicular cancer patients diagnosed over a 4 year period through the rapid case ascertainment system in each state. An equal number of population-based controls (300 from Connecticut and 500 from Massachusetts) will be frequency matched to the cases by age (-5 years) and sex and will be selected by random digit dialing. Cases and controls will be interviewed by trained interviewers to obtain detailed information on major potential risk factors and confounders, such as birth history, lifestyle factors, and medical history. A blood sample will be collected for chemical analyses and for genetic testing. The study laboratories led by Drs. Chen and Altshul, who are currently conducting the genotyping and organochlorine analyses for studies of testicular cancer and other male reproductive disorders, respectively, represent a unique strength of the proposal. Another strength is the large sample size, achieved by conducting the study in two states. This will provide the study with sufficient statistical power to test the hypotheses.